Acute Kidney Injury Following Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma in a Kidney Transplant Recipient

Melilli, Edoardo; Mussetti, Alberto; Linares, Gabriela Sanz; Ruella, Marco; Salette, Charette La; Savchenko, Alexandre; Taco, Maria del Rosario; Montero, Núria; Grinyó, Josep M.; Favà, Àlex; Gomà, Montse; Meneghini, Maria; Manonelles, Anna; Cruzado, Josepmaria; Sureda, A; Bestard, Oriol

doi:10.1016/j.xkme.2021.03.011

Cited by 14 publications

(5 citation statements)

References 19 publications

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“…Despite the post-CAR T-cell-induced renal damage, patients can present with borderline AKI before receiving the therapy, and their creatinine stays within manageable range, especially with axicabtagene ciloleucel [ 15 , 47 ]. The majority of patients with B-cell lymphomas also present with pre-CAR-T cell therapy AKI [ 13 ], though the incidence of AKI after CAR-T cell therapy is low, unless an ICU admission or grade 3–4 CRS occurs [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review

Khan¹,

Khan

Wolfson

et al. 2023

Clin Hematol Int

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Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy targeting specifically cancerous cells, and has been shown to induce durable remissions in some refractory hematological malignancies. However, CAR T-cell therapy has adverse effects, such as cytokine release syndrome (CRS), immune effector-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and acute kidney injury (AKI), among others. Not many studies have covered the repercussions of CAR T-cell therapy on the kidneys. In this review, we summarized the available evidence on the safety profile of CAR T-cell therapy in patients with pre-existing renal insufficiency/AKI and in those who develop AKI as a result of CAR T-cell therapy. With a 30% incidence of AKI post-CAR T-cell, various pathophysiological mechanisms, such as CRS, hemophagocytic lymphohistiocytosis (HLH), TLS, serum cytokines, and inflammatory biomarkers, have been shown to play a role. However, CRS is commonly reported as an underlying mechanism. Overall, 18% of patients in our included studies developed AKI after receiving CAR T-cell therapy, and most cases were reversible with appropriate therapy. While phase-1 clinical trials exclude patients with significant renal toxicity, two studies (Mamlouk et al. and Hunter et al.) reported successful treatment of dialysis-dependent patients with refractory diffuse large B-cell lymphoma, and demonstrated that CAR T-cell therapy and lymphodepletion (Flu/Cy) can be safely administered.

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Section: Discussionmentioning

confidence: 99%

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review

Khan¹,

Khan

Wolfson

et al. 2023

Clin Hematol Int

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“…LDH may be considered as a surrogate marker of tumor burden in these patients who may have kidney infiltration of tumor cells, especially in lymphoma patients with high tumor burden [ 29 ]. AKI secondary to interstitial T cell infiltration have also been described in several case reports, especially in kidney transplant recipients having received CAR-T cell therapy for post-transplant B cell lymphoma [ 13 , 30 ]. However, T cell infiltration in these cases did not correspond to CAR-T infiltration, but primarily involved endogenous CD19 negative T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

“…AKI may also be a consequence of severe sepsis [ 10 , 11 ], or tumor lysis syndrome [ 12 ]. Rare cases of tubule-interstitial nephropathy have also been described [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Acute kidney injury after CAR-T cell therapy: exploring clinical patterns, management, and outcomes

Vincendeau,

Joseph,

Thieblemont

et al. 2024

Clinical Kidney Journal

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Background Acute kidney injury (AKI) has been reported after CAR-T cells, but available data are limited. We sought to describe the incidence of AKI in a cohort of patients hospitalized in the intensive care unit (ICU) following CAR-T cell reinjection, identify the primary factors linked to the onset of AKI, and ascertain the key determinants associated with kidney outcomes and mortality. Methods We retrospectively analyzed 119 patients hospitalized in ICU after CAR-T cell therapy between 2017 and 2023. Factors associated with AKI, mortality, and kidney sequelae were identified using multivariate analyses. Results Of the 119 patients, 41 patients fulfilled diagnostic criteria of AKI (34%). By multivariate analysis, grade ≥3 cytokine release syndrome (CRS) [OR = 1.20 CI95% (1.01–1.43)] and elevated lactate dehydrogenase (LDH) levels at admission [OR = 1.44 CI95% (1.04–1.99)] were significantly associated with the occurrence of AKI during ICU stay. AKI KDIGO ≥2 was an independent risk factor for hospital mortality [OR = 1.50 (1.22–1.85), P < 0.001]. Nine out of 12 (75%) and 6/9 (67%) patients who had experienced AKI and survived had chronic kidney disease (CKD) at 6 months and 1 year, respectively. We did not identify any specific factor associated with kidney recovery. Conclusion AKI may occur in ICU patients receiving CAR-T cell therapy, especially those who experience CRS and exhibit elevated LDH levels. Early recognition of AKI is of utmost importance as it substantially compromises survival in these patients. Future studies should aim to elucidate the underlying pathophysiological mechanisms of AKI in this context and pinpoint predictive factors for long-term risks of CKD.

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“…Mellili et al reported one patient with B-cell-derived lymphoproliferative disease after kidney transplantation of 17 years who received anti-CD19 CAR-T cell therapy due to intolerance to conventional therapy and discontinued all potentially nephrotoxic drugs (omeprazole and acyclovir) [ 54 ]. The data showed a gradual decrease in glomerular filtration rate 12 days after CAR-T infusion in the absence of observable CRS and ICANS.…”

Section: Car-t Cell Therapy-related Kidney Injurymentioning

confidence: 99%

CAR-T Cell Therapy: Advances in Kidney-Related Diseases

Wu,

Feng,

Huang

et al. 2024

Kidney Dis

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Currently, renal malignancies and some diseases accompanied by renal impairment, such as multiple myeloma (MM), systemic lupus erythematosus (SLE), and acquired immunodeficiency syndrome (AIDS) are characterized by encouraging benefits from immunotherapy that have led to significantly improved outcomes. In this regard, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy, which is becoming a hot issue and revealing potential in these diseases. Additionally, with numerous novel targets and indications being discovered and tried for clinical practice, the nephrotoxicity associated with CAR-T cell therapy also needs attention. In this review, we focused on discussing the effects and drawbacks of CAR-T cell therapy in several common diseases involving kidneys, as well as how we might enhance it.

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Acute Kidney Injury Following Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma in a Kidney Transplant Recipient

Cited by 14 publications

References 19 publications

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review

Acute kidney injury after CAR-T cell therapy: exploring clinical patterns, management, and outcomes

CAR-T Cell Therapy: Advances in Kidney-Related Diseases

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